[Effect of erythropoietin 3-enhancer on proliferation of pulmonary artery smooth muscle cells induced by hypoxia].

The effects of erythropoietin (EPO)3 -enhancer on endothelium-dependent and endothelium-independent proliferation caused by hypoxia in cultured porcine pulmonary artery smooth muscle cells (PASMCs) were investigated with MTT test, H(3)-TdR incorporation and flow-cytometry. The results showed that (1) PASMCs exposed to hypoxia for 24 h proliferated significantly, which was suppressed by pretransfecting wild type EPO3 -enhancer fragments into PASMCs, but not by protransfecting mutant fragments; and (2) the conditioned medium of pulmonary artery endothelial cells (PAECs) exposed to hypoxia for 24 h promoted the proliferation of PASMCs. This effect was abolished when wild type EPO3 -enhancer fragments were transfected, but it persisted when mutant fragments were transfected. The results suggest that (1) the conditioned medium of hypoxic PAECs induces proliferation of PASMCs. This may be because that not only PAECs are sensitive to hypoxia, but also PASMCs respond to hypoxia directly; and the hypoxic responses of both endothelial cells (ECs) and smooth muscle cells (SMCs) can be inhibited by exogenous EPO3 -enhancer fragments. (2) Since there is a HIF-1 binding site in EPO3 -enhancer, there may be a common pathway for HIF-1 hypoxia signal transduction in hypoxic responses of ECs and SMCs.